Human beings have had a long battle against cancer. Because the disease is so widespread, manifests itself in so many different ways and is so relentless, the potential market for effective cancer therapies is enormous. It is estimated that 10 million people in the U.S. either have or have had cancer. The National Cancer Institute (NCI) projected that in 1995, some 1.2 million new cases of cancer will be diagnosed in the United States, and that 538,000 people will die of the disease.
Cancer is currently treated, with a low degree of success, with combinations of surgery, chemotherapy and radiation. The reason for the low degree of success in chemotherapy is because current chemotherapeutic approaches target rapidly dividing tumor cells. This approach is ineffective against cancer that is dormant or slow growing. Such treatments also affect other, noncancerous cells that divide rapidly, thereby causing harmful side effects.
Recently, a new approach has emerged in the battle against cancer. This approach is based on the biological phenomenon called “Apoptosis”. Apoptosis is also called “programmed cell death” or “cell suicide”. (Krammer, et al., “Apoptosis in the APO-1 System”, Apoptosis: The molecular Basis of Cell Death, pp. 87-99 Cold Spring Harbor Laboratory Press, 1991). In contrast to the cell death caused by cell injury, apoptosis is an active process of gene-directed, cellular self-destruction that serves a biologically meaningful function. (Kerr, J. F. R and J. Searle J. Pathol. 107:41, 1971). One example of the biologically meaningful function of apoptosis occurs during the morphogenesis of an embryo. (Michaelson, J. Biol. Rev. 62:115, 1987). Just as the sculpting of a sculpture needs the addition as well as removal of clay, the organ formation (Morphogenesis) of an embryo relies on cell growth (addition of clay) as well as cell death (removal of clay). As a matter of fact, apoptosis plays a key role in the human body from the early stages of embryonic development through to the inevitable decline associated with old age. (Wyllie, A. H. Int. Rev. Cytol. 68:251, 1980). The normal functioning of the immune, gastrointestinal, and hematopoietic systems depend upon the normal function of apoptosis. When the normal function of apoptosis goes awry, the result can be one of a number of diseases including cancer, viral infections, auto-immune disease/allergies, neurodegeneration, or cardiovascular diseases. Because of the role apoptosis plays in human diseases, apoptosis is becoming a prominent buzzword in the pharmaceutical research field. Huge amounts of time and money are being spent in an attempt to understand how it works, how it can be encouraged or inhibited, and what this means for practical medicine. A handful of companies have been formed with the prime direction of turning work in this nascent field into marketable pharmaceutical products. The emergence of a core of innovative young companies combined with the steps being taken by established industrial players are certain to make apoptosis research one of the fastest-growing and most promising areas of medical study.
The idea that cancer may be caused by insufficient apoptosis first arose in the early 1990's (Cope, F. O. and Wille, J. J., “Apoptosis”: The Molecular Basis of Cell Death, Cold Spring Harbor Laboratory Press, p. 61, 1991). This idea opened a door for a new concept in cancer therapy—Cancer cells may be killed by encouraging apoptosis. Apoptosis modulation, based on the processes present in normal development, is a potential mechanism for controlling the growth of tumor cells. Inducing apoptosis in tumor cells is an attractive approach because, at least in theory, it would teach the cells to commit suicide. Nevertheless, since the objective of cancer treatment is to kill cancer cells without killing the host, the success of this treatment is still dependent on the availability of drugs that can selectively induce apoptosis in tumor cells without affecting normal cells. In this patent application, the apoptotic activity of naturally occurring fetuin (which has been modified), chemically synthesized fetuin, recombinant fetuin, and their associated fragments upon cancer cells are elucidated. In addition, the effects of alpha 2 and associated fragments are expounded. These proteins and polypeptides may present a new class of anticancer drugs that induce apoptosis in cancer cells, which may offer a breakthrough in cancer therapy.